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National Institute of Cholera & Enteric Diseases, Kolkata, India; Infectious Diseases & Immunology Division, Indian Institute of Chemical Biology, Kolkata, India
* To whom correspondence should be addressed. Email:
chatterjeens{at}icmr.org.in; nschatterjee@rediffmail.com.
The chitin-binding protein GbpA of Vibrio cholerae has been recently described as a common adherence factor for chitin and intestinal surface. Using an isogenic in-frame gbpA deletion mutant, we first show that V. cholerae O1 El Tor interacts with mouse intestinal mucus quickly, using GbpA in a specific manner. The gbpA mutant strain showed significant decrease in intestinal adherence, leading to less colonization and fluid accumulation in a mouse in vivo model. Purified recombinant GbpA (rGbpA) specifically bound to N-acetyl-D-glucosamine residues of intestinal mucin in a dose-dependent, saturable manner with a Kd of 11.2 µM. Histopathology results from infected mouse intestine indicated that GbpA binding resulted in a time-dependent increase in mucus secretion. We found that rGbpA increased the production of intestinal secretory mucins (MUC2, MUC3 and MUC5AC) in HT-29 cells through upregulation of corresponding genes. The upregulation of MUC2 and MUC5AC genes was dependent on NF-
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
INTESTINAL ADHERENCE OF VIBRIO CHOLERAE INVOLVES A COORDINATED INTERACTION BETWEEN COLONIZATION FACTOR GbpA AND MUCIN
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B nuclear translocation. Interestingly, mucin could also increase GbpA expression in V. cholerae in a dose-dependent manner. Thus, we propose that there is a coordinated interaction between GbpA and mucin to up-regulate each other in a cooperative manner, leading to increased levels of expression of both of these interactive factors, ultimately allowing successful intestinal colonization and pathogenesis by V. cholerae.
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